Monocytes, macrophages and the RES constitute a derivative of the original host defense system of multicellular organisms. In recent years, this system has been shown to selectively recognize tumor cells and have the capacity to destroy them in vitro. There is considerable evidence in animals models that this system plays a major role in anti-tumor host defense and indeed, administration of macrophage activators or of activated macrophages themselves can control tumor growth. However, activated macrophages may have detrimental effects because they may actually nurture tumor growth or serve as suppressor cells under certain circumstances. Relatively little research has been done on this system in human cancer patients. With the availability of drugs which can depress or augment monocyte-macrophage- and RES function, it seems essential to characterize this system in man and the in vitro and in vivo effects of drugs on it. This would result in a better understanding of the role of the system in the natural history and response to therapy and also lead to the development of better treatment strategy. Specifically, we will conduct a series of assays of monocyte-macrophage-RES activity in human cancer patients including RES particle clearance (of RhD coated autologous erythrocytes), monocyte tumoricidal activity, monocyte ectoenzymes, monocyte-mediated ADCC, monocyte adherence and monocyte-mediated suppressor cell activity in cancer patients of different types, receiving chemotherapy and biological therapy. The latter will include leukocyte interferon, fibroblast interforan, recombinant DNA-produced interferon, poly ICLC, pyran copolymer derivatives and low molecular weight pyrimidinole interferon inducers. Changes induced in the various functions will be studied for mechanism of action including changes in effector cell number, Fc receptor expression, target cell binding, ectoenzyme content, lytic unit expression and suppressor cell activity. The data generated should result in a general understanding of the role of this system in antitumor host defense, a standardized system for quantitating and the monitoring the activity of macrophage activating drugs and for the optimal development of them for clinical therapeutics.